Isabel Gonzalo

Steele-Richardson-Olszewski syndrome in a patient with a single C212Y mutation in the parkin protein.

Steele‐Richardson‐Olszewski syndrome (SROS) is a neurodegenerative disorder of unknown aetiology, most frequently sporadic. Familial cases of SROS have been described. An intronic polymorphism of the tau gene is associated with sporadic SROS and mutations of the tau gene are present in atypical cases of SROS. The role of tau has been excluded in other families with pathology proven SROS, suggesting that this syndrome may have multiple causes. An 82‐year‐old patient, father of 3 children with autosomal recessive juvenile parkinsonism due to combined heterozygous mutations of the parkin gene, developed clinical features of SROS 2 years before death. The diagnosis was confirmed by pathology. He carried the C212Y mutation of the parkin gene and was homozygous for the A0 polymorphism and for the H1 haplotype. The role of parkin in the processing of tau is discussed.

Patterns of protein nitration in dementia with Lewy bodies and striatonigral degeneration

Abstract. The synucleinopathies are a group of neurodegenerative disorders characterized by the presence of α-synuclein inclusions in neurons (Lewy body diseases, LBD) or glial cells (multiple system atrophies, MSA). Recently, nitration of α-synuclein has been reported as the possible modification that induces its aggregation and deposition in these disorders. In this study we investigated the distribution and relationships of α-synuclein inclusions and 3-nitrotyrosine (3-NT), a marker of protein nitration through oxidative mechanisms, in brains diagnosed with LBD or MSA and control brains using double immunohistochemical techniques. In LBD cases, 3-NT colocalized with α-synuclein immunoreactivity in classic and cortical Lewy bodies and in dystrophic neurites in substantia nigra. However, most pale bodies and diffuse deposits in substantia nigra and Lewy neurites in hippocampus lack 3-NT immunoreactivity. A majority of cases showed diffuse cytoplasmic 3-NT staining in pyramidal cells of the CA2–3 regions of the hippocampus that was independent of α-synuclein deposits. All MSA cases showed 3-NT immunoreactivity in glial inclusions. 3-NT neuronal staining was restricted to pontine nuclei with three cases showing nuclear and one case cytoplasmic staining. There was no colocalization of 3-NT nuclear immunoreactivity with α-synuclein-immunopositive nuclear inclusions in pontine neurons. These data show that protein nitration in LBD and MSA cases has a widespread distribution and is not only associated with the α-synuclein deposits. The presence of α-synuclein-positive deposits lacking 3-NT immunoreactivity suggests that nitration is not a prerequisite for α-synuclein deposition.

Progressive supranuclear palsy and tau hyperphosphorylation in a patient with a C212Y parkin mutation

Autosomal recessive-juvenile parkinsonism (AR-JP) is one of the most common forms of familial Parkinsons disease (PD) and is related to mutations in the Park-2 gene, encoding for a protein ligase of ubiquitin, parkin. Different mutations located along the parkin gene have been observed in different AR-JP affected families, possibly interfering with the normal function of parkin and the proteasome system. Two cases of patients with AR-JP have been recently described presenting different homo- and heterozygous parkin mutations and limited tau pathology. We report here the case of a patient with clinical and pathological findings compatible with progressive supranuclear palsy (PSP), carrier of a single, heterozygous mutation of the parkin gene, and homozygous for the H1/H1 haplotype in the tau gene. Abnormal tau hyperphosphorylation has been observed in our patient brain samples, suggesting that a partial deficit of parkin, a protein with ubiquitin-ligase function, may trigger tau pathology in individuals with molecular genetic risk factors.

Control of temporal characteristics of Bessel-X pulses in dispersive media

We study Bessel-X pulses with dispersion in the cone angle that propagate without temporal spreading in a medium with group velocity dispersion (GVD). The general conditions for GVD-free propagation are given. Previously known results are encompassed as particular cases. We show that general GVD-free Bessel-X pulses, propagating at controlled phase and group velocities in the medium, can be generated in practice by means of an axicon and a circular diffraction grating.

Effects of fibroblast growth factor and glial-derived neurotrophic factor on akinesia, F-DOPA uptake and dopamine cells in parkinsonian primates

Parkinsons disease (PD) is a common neurodegenerative disorder that produces progressive disability despite symptomatic treatment. Several strategies, including stereotaxic brain lesions, deep brain stimulation, transplants of dopamine cells and administration of neurotrophic factors, have been proposed to improve efficacy and to counteract the progression of the disease. We here report the effects of repetitive intracerebral infusion of basic fibroblast growth factor (bFGF) and glial-derived neurotrophic factor, up to 1 year, in Cynomolgus monkeys with long standing asymmetric parkinsonism produced by unilateral intracarotid injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The treatment with neurotrophic factors was initiated when the parkinsonian deficits were stable, 6 months after the administration of MPTP. The evaluation of the response to the neurotrophic factors was performed by blind observers using: clinical scales that measured global motor deficit, motor ability in both hands, apomorphine-induced rotation, determination of the levels of monoamine metabolites in cerebrospinal fluid, and 6-F18-fluoro-l-DOPA (F-DOPA) uptake in the striatum and histology. Both factors, but bFGF more so, improve motor behavior, dopamine metabolism, striatal F-DOPA uptake, and the number of dopamine neurons. The procedure is well tolerated and provides a strong background for efficacy and safety of this treatment in patients with PD.

Time-Dispersive Effects in the J. Gonzalo's Research on Cerebral Dynamics

In the present work, certain aspects, restricted to the visual system, of the J. Gonzalos research, are interpreted according to a simple linear theory of time-dispersion applied to the dynamic cerebral system, characterized by its excitability and its reaction velocity.

Pulsed light beams in vacuum with superluminal and negative group velocities

We study the group velocity of pulsed light beams in vacuum. Gouys phase associated with the diffraction of transversally limited pulses can create a strong anomalous dispersion in vacuum leading to highly superluminal and negative group velocities. As a consequence, a focusing pulse can diverge beyond the focus before converging into it. The experimental feasibility is discussed.

Zeno dynamics in wave-packet diffraction spreading

We analyze a simple and feasible practical scheme displaying Zeno, anti-Zeno, and inverse-Zeno effects in the observation of wave-packet spreading caused by free evolution. The scheme is valid both in spatial diffraction of classical optical waves and in time diffraction of a quantum wave packet. In the optical realization, diffraction spreading is observed by placing slits between a light source and a light-power detector. We show that the occurrence of Zeno or anti-Zeno effects depends just on the frequency of observations between the source and detector. These effects are seen to be related to the diffraction mode theory in Fabry-Perot resonators.

Intersensorial summation as a nonlinear contribution to cerebral excitation

Visual deficits have been discovered in sufferers of Parkinsons disease [1] and the cause of this is not clearly understood. This paper reports on a digital neuromodel that investigates a hypothesis that the deficit may be due to a projection from the Basal Ganglia to the Superior Colliculus where a shortage of Dopamine introduces noise in the oculo-motor loop. New experiments were done with Parkinsons patients to track the deficit and the neuromodel predicts performance against oculo-motor noise. It is seen that a group Parkinsons sufferers in whom the deficit is pronounced follow the predicted law, while controls with poor performance do not follow the law. This helps to uphold the noise hypothesis.

Gouy wave modes: undistorted pulse focalization in a dispersive medium

Gouy wave modes are linear waves with finite energy that propagate without distortion at any phase and group velocity through a focal region in a dispersive medium. These features make them potentially useful for the onset and control of nonlinear interactions.